Understanding the pathogenesis of aspiration pneumonitis at the cellular and molecular level is important in the development of strategies to decrease the severity of lung injury following aspiration of gastric contents. The role of the neutrophil as the primary effector cell involved in aspiration-induced inflammatory lung injury is the primary direction of these experiments. The role of the macrophage, endothelium and alveolar epithelium in the regulation of the injury will also be explored. Using intrapulmonary deposition of three possible combinations of gastric contents, etiologically-linked to aspiration pneumonitis (low pH, gastric particulate, or low pH plus particulate), these investigators will assess in Aim #1 the role of TNF(, IL-1, MIP-2, and MCP-1 in the recruitment and activation of inflammatory cells in the rat by employing functional assays, ELISAs, and Northern assays, as well as blocking antibodies and other inhibitors of cytokine activity. The kinetics of the cascade, the requirement in the pathogenesis of the lung injury, and cytokine-cytokine dependency are the major objectives of this aim. In Aim #2 they will extend preliminary studies examining the role of MOs, alveolar epithelial cells, and pulmonary endothelial cells in the "triggering" of the inflammatory injury in the three aspiration models by examining indices of cell function, expression of adhesion molecules, and generation of proinflammatory cytokines in cells isolated after injury following intrapulmonary deposition of different aspirates. They will also assess the ability of increased [H+] and/or gastric particles to stimulate these cells, in vitro. In Aim #3 the investigators will examine the role of IL-10 in the regulation of the inflammatory injury following instillation of the three possible combinations of gastric contents by examining upregulation of IL-10 expression and the ability of anti-IL-10 antibody to alter the severity of the lung injury and other cytokine expression. They will also assess the effects of intratracheally administered IL-10 on lung injury, proinflammatory cytokine responses, and adhesion molecule expression. In Aim #4 the investigators will continue to pursue their studies examining the role of L-arginine in the pathogenesis of the aspiration-induced lung injury by directly measuring indices of activity, iNOS expression, and selective inhibition of the mediators. The interaction of factors that control the production of peroxinitrites, will also be explored.